Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study
Abstract Background Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. Methods Using data from the German multi-center E-HIT-REZ-2005 study, we examined...
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| Veröffentlicht in: | Neuro-oncology (Charlottesville, Va.) Va.), 2021-06, Vol.23 (6), p.1012-1023 |
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| creator | Adolph, Jonas E Fleischhack, Gudrun Mikasch, Ruth Zeller, Julia Warmuth-Metz, Monika Bison, Brigitte Mynarek, Martin Rutkowski, Stefan Schüller, Ulrich von Hoff, Katja Obrecht, Denise Pietsch, Torsten Pfister, Stefan M Pajtler, Kristian W Witt, Olaf Witt, Hendrik Kortmann, Rolf-Dieter Timmermann, Beate Krauß, Jürgen Frühwald, Michael C Faldum, Andreas Kwiecien, Robert Bode, Udo Tippelt, Stephan |
| description | Abstract
Background
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
Methods
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.
Results
Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.
Conclusion
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%). |
| doi_str_mv | 10.1093/neuonc/noaa276 |
| format | Article |
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Background
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
Methods
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.
Results
Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.
Conclusion
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noaa276</identifier><identifier>PMID: 33331885</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Brain Neoplasms - drug therapy ; Child ; Clinical Investigations ; Ependymoma - drug therapy ; Humans ; Neoplasm Recurrence, Local - drug therapy ; Radiotherapy, Adjuvant ; Retrospective Studies ; Temozolomide</subject><ispartof>Neuro-oncology (Charlottesville, Va.), 2021-06, Vol.23 (6), p.1012-1023</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-b3c34b193ee643e19324f483aa7f2ecc67ab06c662d0efc7188471ec8d9291453</citedby><cites>FETCH-LOGICAL-c424t-b3c34b193ee643e19324f483aa7f2ecc67ab06c662d0efc7188471ec8d9291453</cites><orcidid>0000-0002-3544-319X ; 0000-0002-8952-1819 ; 0000-0001-5849-8671</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168820/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168820/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1584,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33331885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adolph, Jonas E</creatorcontrib><creatorcontrib>Fleischhack, Gudrun</creatorcontrib><creatorcontrib>Mikasch, Ruth</creatorcontrib><creatorcontrib>Zeller, Julia</creatorcontrib><creatorcontrib>Warmuth-Metz, Monika</creatorcontrib><creatorcontrib>Bison, Brigitte</creatorcontrib><creatorcontrib>Mynarek, Martin</creatorcontrib><creatorcontrib>Rutkowski, Stefan</creatorcontrib><creatorcontrib>Schüller, Ulrich</creatorcontrib><creatorcontrib>von Hoff, Katja</creatorcontrib><creatorcontrib>Obrecht, Denise</creatorcontrib><creatorcontrib>Pietsch, Torsten</creatorcontrib><creatorcontrib>Pfister, Stefan M</creatorcontrib><creatorcontrib>Pajtler, Kristian W</creatorcontrib><creatorcontrib>Witt, Olaf</creatorcontrib><creatorcontrib>Witt, Hendrik</creatorcontrib><creatorcontrib>Kortmann, Rolf-Dieter</creatorcontrib><creatorcontrib>Timmermann, Beate</creatorcontrib><creatorcontrib>Krauß, Jürgen</creatorcontrib><creatorcontrib>Frühwald, Michael C</creatorcontrib><creatorcontrib>Faldum, Andreas</creatorcontrib><creatorcontrib>Kwiecien, Robert</creatorcontrib><creatorcontrib>Bode, Udo</creatorcontrib><creatorcontrib>Tippelt, Stephan</creatorcontrib><title>Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study</title><title>Neuro-oncology (Charlottesville, Va.)</title><addtitle>Neuro Oncol</addtitle><description>Abstract
Background
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
Methods
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.
Results
Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.
Conclusion
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).</description><subject>Adolescent</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Child</subject><subject>Clinical Investigations</subject><subject>Ependymoma - drug therapy</subject><subject>Humans</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Radiotherapy, Adjuvant</subject><subject>Retrospective Studies</subject><subject>Temozolomide</subject><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERUvhyhH5CAe3tuM4DgekqlpopZUqVeXCxfI6k26QYwfbQco_4Gfj_aCCU-cyo_E7j2f0IvSO0QtG2-rSwxy8vfTBGN7IF-iM1bwitZLy5b7mRNWsOUWvU_pBKWe1ZK_QaVWCKVWfod_rYI3Dxnc4LSnDOFictxDNtODQ4wh2jhF8xjCB75YxjAYPHtvt4LrS3w-aLjhItqjSJ5y2IWay77vgH0mGOBZMml1OO2KB4xW5uX0g96vvmFNa45TnbnmDTnrjErw95nP07cvq4fqGrO--3l5frYkVXGSyqWwlNqytAKSooBRc9EJVxjQ9B2tlYzZUWil5R6G3TblSNAys6lreMlFX5-jzgTvNmxG63dbROD3FYTRx0cEM-v8XP2z1Y_ilFZNKcVoAH46AGH7OkLIeh3K8c8ZDmJPmoqEt5UKxIr04SG0MKUXon75hVO_s0wf79NG-MvD-3-We5H_9KoKPB0GYp-dgfwCVc6jC</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Adolph, Jonas E</creator><creator>Fleischhack, Gudrun</creator><creator>Mikasch, Ruth</creator><creator>Zeller, Julia</creator><creator>Warmuth-Metz, Monika</creator><creator>Bison, Brigitte</creator><creator>Mynarek, Martin</creator><creator>Rutkowski, Stefan</creator><creator>Schüller, Ulrich</creator><creator>von Hoff, Katja</creator><creator>Obrecht, Denise</creator><creator>Pietsch, Torsten</creator><creator>Pfister, Stefan M</creator><creator>Pajtler, Kristian W</creator><creator>Witt, Olaf</creator><creator>Witt, Hendrik</creator><creator>Kortmann, Rolf-Dieter</creator><creator>Timmermann, Beate</creator><creator>Krauß, Jürgen</creator><creator>Frühwald, Michael C</creator><creator>Faldum, Andreas</creator><creator>Kwiecien, Robert</creator><creator>Bode, Udo</creator><creator>Tippelt, Stephan</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3544-319X</orcidid><orcidid>https://orcid.org/0000-0002-8952-1819</orcidid><orcidid>https://orcid.org/0000-0001-5849-8671</orcidid></search><sort><creationdate>20210601</creationdate><title>Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study</title><author>Adolph, Jonas E ; Fleischhack, Gudrun ; Mikasch, Ruth ; Zeller, Julia ; Warmuth-Metz, Monika ; Bison, Brigitte ; Mynarek, Martin ; Rutkowski, Stefan ; Schüller, Ulrich ; von Hoff, Katja ; Obrecht, Denise ; Pietsch, Torsten ; Pfister, Stefan M ; Pajtler, Kristian W ; Witt, Olaf ; Witt, Hendrik ; Kortmann, Rolf-Dieter ; Timmermann, Beate ; Krauß, Jürgen ; Frühwald, Michael C ; Faldum, Andreas ; Kwiecien, Robert ; Bode, Udo ; Tippelt, Stephan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-b3c34b193ee643e19324f483aa7f2ecc67ab06c662d0efc7188471ec8d9291453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Child</topic><topic>Clinical Investigations</topic><topic>Ependymoma - drug therapy</topic><topic>Humans</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Radiotherapy, Adjuvant</topic><topic>Retrospective Studies</topic><topic>Temozolomide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adolph, Jonas E</creatorcontrib><creatorcontrib>Fleischhack, Gudrun</creatorcontrib><creatorcontrib>Mikasch, Ruth</creatorcontrib><creatorcontrib>Zeller, Julia</creatorcontrib><creatorcontrib>Warmuth-Metz, Monika</creatorcontrib><creatorcontrib>Bison, Brigitte</creatorcontrib><creatorcontrib>Mynarek, Martin</creatorcontrib><creatorcontrib>Rutkowski, Stefan</creatorcontrib><creatorcontrib>Schüller, Ulrich</creatorcontrib><creatorcontrib>von Hoff, Katja</creatorcontrib><creatorcontrib>Obrecht, Denise</creatorcontrib><creatorcontrib>Pietsch, Torsten</creatorcontrib><creatorcontrib>Pfister, Stefan M</creatorcontrib><creatorcontrib>Pajtler, Kristian W</creatorcontrib><creatorcontrib>Witt, Olaf</creatorcontrib><creatorcontrib>Witt, Hendrik</creatorcontrib><creatorcontrib>Kortmann, Rolf-Dieter</creatorcontrib><creatorcontrib>Timmermann, Beate</creatorcontrib><creatorcontrib>Krauß, Jürgen</creatorcontrib><creatorcontrib>Frühwald, Michael C</creatorcontrib><creatorcontrib>Faldum, Andreas</creatorcontrib><creatorcontrib>Kwiecien, Robert</creatorcontrib><creatorcontrib>Bode, Udo</creatorcontrib><creatorcontrib>Tippelt, Stephan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adolph, Jonas E</au><au>Fleischhack, Gudrun</au><au>Mikasch, Ruth</au><au>Zeller, Julia</au><au>Warmuth-Metz, Monika</au><au>Bison, Brigitte</au><au>Mynarek, Martin</au><au>Rutkowski, Stefan</au><au>Schüller, Ulrich</au><au>von Hoff, Katja</au><au>Obrecht, Denise</au><au>Pietsch, Torsten</au><au>Pfister, Stefan M</au><au>Pajtler, Kristian W</au><au>Witt, Olaf</au><au>Witt, Hendrik</au><au>Kortmann, Rolf-Dieter</au><au>Timmermann, Beate</au><au>Krauß, Jürgen</au><au>Frühwald, Michael C</au><au>Faldum, Andreas</au><au>Kwiecien, Robert</au><au>Bode, Udo</au><au>Tippelt, Stephan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><addtitle>Neuro Oncol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>23</volume><issue>6</issue><spage>1012</spage><epage>1023</epage><pages>1012-1023</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract
Background
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
Methods
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.
Results
Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.
Conclusion
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33331885</pmid><doi>10.1093/neuonc/noaa276</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3544-319X</orcidid><orcidid>https://orcid.org/0000-0002-8952-1819</orcidid><orcidid>https://orcid.org/0000-0001-5849-8671</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); PubMed Central |
| subjects | Adolescent Brain Neoplasms - drug therapy Child Clinical Investigations Ependymoma - drug therapy Humans Neoplasm Recurrence, Local - drug therapy Radiotherapy, Adjuvant Retrospective Studies Temozolomide |
| title | Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study |
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